crossing96/oncoscreening huggingface dataset:
Impact of Histological Variants on Clinical Responses to Pembrolizumab in Patients With Metastatic Urothelial Cancer.	BACKGROUND: The efficacy of anti-programmed celldeath protein 1 treatment in patients with urothelial carcinoma (UC) with molecular subtypes of histological variants has not been investigated. This study aimed to examine the impact of histological variants classified according to molecular subtypes on clinical outcomes in patients with platinum-resistant metastatic UC treated with pembrolizumab. PATIENTS AND METHODS: Data of 168 patients with metastatic UC who received intravenous pembrolizumab after platinum-based chemotherapy between December 2017 and November 2020 were retrospectively reviewed. Relationships between histological variant type (basal or luminal molecular subtypes) and survival outcome and response to immunotherapy were examined. Clinicopathological factors were analyzed using the Cox proportional hazards model. RESULTS: UC with histological variants was identified in 19 (11.3%) cases (basal subtype in 12; luminal subtype in 7). The median age of the patients was 72.5 years (range=40-89 years). The performance status was 0-1 in 151 (89.9%) patients. Liver metastasis was detected in 44 (26.2%) patients. The median progression-free survival was 3.5 months (range=0.5-34.3 months). Treatment with immune checkpoint inhibitors resulted in an overall mean survival (from the start of treatment) of 8.1 months (range=1.2-34.3 months). Patients with basal-type UC had significantly shorter progression-free survival and cancer-specific survival than those with pure UC (p=0.010 and p=0.035, respectively). A complete response was observed in eight patients (seven with pure UC, one with basal type). CONCLUSION: The basal histological variant might be a potential prognostic indicator in patients with platinum-resistant metastatic UC treated with pembrolizumab.	bladder
Synchronous Penile Squamous Cell Carcinoma, Bladder Urothelial Carcinoma and Prostate Adenocarcinoma Diagnosed in One Procedure.	BACKGROUND: The synchronous diagnoses of three primary malignancies in a patient is rare and represents a difficult treatment challenge. We report a rare case of an 81-year-old male with synchronous triple urogenital cancers including penile squamous cell carcinoma, bladder papillary urothelial carcinoma, and prostate adenocarcinoma. CASE REPORT: The patients presented with a penile lesion with blood draining through the foreskin. Further examination with cystoscopy during the biopsy procedure revealed a 1.5-cm tumor along the left lateral bladder wall and a firm prostate in bilateral lobes. Diagnosis of penile squamous cell carcinoma was confirmed by biopsies of the penile lesions and glans as confirmed by cystoscopy and histological evaluation of the tissue obtained by transurethral resection of the bladder. Biopsies of the prostatic urethra confirmed a diagnosis of prostate adenocarcinoma. All biopsies were performed in a single procedure. Pathology findings revealed moderately differentiated squamous cell carcinoma (p16+) invading the lamina propria of the glans penis, noninvasive low-grade papillary urothelial carcinoma of the bladder, and high-grade prostatic adenocarcinoma (Gleason score 5+5=10) within the prostatic stroma. CONCLUSION: Review of the English literature through PubMed search suggests that this specific combination of synchronous triple urogenital cancer is the first documented case of its kind. Incidence, diagnosis, and treatment for the combination of these cancer types are discussed with consideration for concurrent management of three primary cancers.	bladder
Can We Predict a Higher Risk of Urothelial Bladder Cancer With a Simple Blood Test?	BACKGROUND/AIM: The COVID-19 pandemic highlighted the need to develop tools prioritizing high risk patients for urgent evaluation. Our objective was to determine whether Glasgow Prognostic Score (GPS), an inflammation-based score, can predict higher grade and stage urothelial bladder cancer in patients with gross hematuria who need urgent evaluation. PATIENTS AND METHODS: We analyzed a database of 129 consecutive patients presenting with gross hematuria. GPS was calculated using pretreatment C-reactive protein (CRP) and albumin levels. Patients with bacteriuria or other known malignancies were excluded. The relationship between GPS and final diagnosis was analyzed with multivariate logistic regression. RESULTS: A total of 101 patients were included in the study and 24 patients were identified without any pathology and 77 with a bladder tumor. Pathology demonstrated 21 with muscle invasive, 18 with high grade non-muscle invasive, and 38 with low grade superficial bladder cancer. Twenty-six of 39 (67%) patients with high grade tumors had a GPS of 1 or 2 compared to only 8 out of 62 (13%) patients with either low grade or negative findings (p<0.0001). Ten of 21 (48%) patients with muscle invasive disease had a GPS of 2 compared to 1 out of 18 (6%) with high grade non muscle invasive tumors (p=0.04). On multivariate analysis, GPS was a strong independent predictor of high grade and stage bladder cancer. CONCLUSION: GPS may serve as a highly accessible predictor of high grade, high stage, and large urothelial bladder tumors at the time of initial evaluation and can help identify patients who need urgent evaluation.	bladder
"The incorrect use of CD75 as a synonym for ST6GAL1 has fostered the expansion of commercial ""ST6GAL1"" antibodies that do not recognize ST6GAL1."	"The ST6GAL1 Golgi sialyltransferase is upregulated in many human malignancies, however, detection of ST6GAL1 protein in cancer tissues has been hindered by the prior lack of antibodies. Recently, numerous commercial antibodies for ST6GAL1 have become available, however, many of these do not, in fact, recognize ST6GAL1. Decades ago, the CD75 cell-surface epitope was mistakenly suggested to be the same molecule as ST6GAL1. While this was rapidly disproven, the use of CD75 as a synonym for ST6GAL1 has persisted, particularly by companies selling ""ST6GAL1"" antibodies. CD75 is reportedly a sialylated epitope which appears to encompass a range of glycan structures and glycan carriers. In this study, we evaluated the LN1 and ZB55 monoclonal antibodies, which are advertised as ST6GAL1 antibodies but were initially developed as CD75-recognizing antibodies (neither was raised against ST6GAL1 as the immunogen). Importantly, the LN1 and ZB55 antibodies have been widely used by investigators, as well as the Human Protein Atlas database, to characterize ST6GAL1 expression. Herein, we used cell and mouse models with controlled expression of ST6GAL1 to compare LN1 and ZB55 with an extensively validated polyclonal antibody to ST6GAL1. We find that LN1 and ZB55 do not recognize ST6GAL1, and furthermore, these 2 antibodies recognize different targets. Additionally, we utilized the well-validated ST6GAL1 antibody to determine that ST6GAL1 is overexpressed in bladder cancer, a finding that contradicts prior studies which employed LN1 to suggest ST6GAL1 is downregulated in bladder cancer. Collectively, our studies underscore the need for careful validation of antibodies purported to recognize ST6GAL1."	bladder
Fibroblast activation protein (FAP) expression in CK5/6 expressed (Basal subtype) & CK20 expressed (Luminal subtype) urothelial bladder carcinoma: an immunohistochemical study.	Urinary bladder cancer incidence varies all over the world. Egypt displays high incidence rates. Molecular subtyping helps risk stratification and personalized treatment. Cancer-associated fibroblasts (CAFs) in the tumor microenvironment may provoke tumor-promotion or tumor suppression. Fibroblast activation protein (FAP) is a marker of CAFs, suggested to accelerate tumor progression in various cancers. In urothelial carcinoma, investigations regarding impact of FAP expression on prognosis are needed. This work aims to study impact of FAP expression in urothelial carcinoma and find its relation to CK 5/6 (basal) expressed and CK 20 (luminal) expressed immunohistochemical markers. This retrospective study included 70 urothelial carcinoma specimens. Immunohistochemistry was performed and results were analyzed. FAP was expressed in 67.1% of cases and showed significant association with advanced tumor stage, muscle invasion, mitoses in tumor cells and stratified groups; as 73.9% of FAP positive cases were of Ck5/6+/Ck20- (basal subtype). All studied parameters did not show significant association with patient's overall survival. In conclusion, FAP could have a role in modulating tumor microenvironment and promoting tumor invasion. FAP is correlated with basal subtype of urothelial carcinoma, which may be an indicator of tumor aggressiveness. FAP antagonists may be helpful in preventing tumor progression.	bladder
Comprehensive analysis of autophagy related long non-coding RNAs in prognosis, immunity, and treatment of muscular invasive bladder cancer.	To predict disease outcome in muscle-invasive bladder cancer (MIBC), we constructed a prognostic autophagy-related (PAR) lncRNA signature. Comprehensive bioinformatics analyses were performed using data from TCGA and GTEx databases. Univariate Cox, and least absolute shrinkage and selection operator regression analyses were also performed, based on differentially expressed genes, to identify PAR-related lncRNAs to establish the signature. Furthermore, the Kaplan-Meier OS curve and receiver operating characteristic curve analyses were performed and a nomogram was constructed, all of which together confirmed the strong predictive ability of the constructed signature. Patients with MIBC were then divided into high- and low-risk groups. Gene enrichment and immune infiltration analyses revealed the potential mechanisms in MIBC. We also further evaluated the signature of molecules related to immune checkpoints and the sensitivity toward chemotherapeutic agents and antitumor-targeted drugs to find better treatment prescriptions. We identified a number of PAR-related lncRNA signatures, including HCP5, AC024060.1, NEAT1, AC105942.1, XIST, MAFG-DT, and NR2F1-AS1, which could be valuable prognostic tools to develop more efficient, individualized drug therapies for MIBC patients.	bladder
CD93 orchestrates the tumor microenvironment and predicts the molecular subtype and therapy response of bladder cancer.	BACKGROUND: CD93 is newly reported to normalize vasculature and attenuate pancreatic cancer therapy response, but its role in bladder cancer (BLCA) is unknown. METHOD: The immunologic role of CD93 is analyzed across TCGA pan-cancers. The correlation between CD93 and BLCA clinical and tumor microenvironment features, predicted immunotherapy pathways, molecular subtypes, therapeutic signatures and mutation status was evaluated in TCGA-BLCA and other two BLCA cohorts. The impact of CD93 on immunotherapy response was validated by five real-world cohorts, and chemotherapy response was assessed with IC50. CD93-based risk model was constructed with LASSO regression and validated by seven independent cohorts. RESULT: CD93 is positively correlated with immunomodulators, tumor-infiltrating lymphocytes (TILs) and immune checkpoints across pan-cancers. In BLCA, CD93 leads to higher T cell inflamed score and expression of immune checkpoints. However, CD93 is indicative of more aggressive clinical features, worse survival, more tumor-associated macrophages and regulatory T cells recruitment, less recognition and killing of cancer cells by T cells, lower predicted chemotherapy and immunotherapy response, which is further validated by immunotherapy cohorts (IMvigor210: 16.11% vs 29.53%; GSE176307: 15.56% vs 20.93%). Notably, CD93 correlates with enriched neuroendocrine subtype and epithelial-mesenchymal transition differentiation, while CD93-low group has enriched luminal subtype. Pathways including hypoxia and Wnt-β-catenin are enriched along with CD93 expression, and more frequent FGFR3 mutation is also observed. Lastly, the CD93-based risk model, validated by seven independent cohorts, is powerful in distinguishing the survival probability of BLCA (3-year AUC 0.808). CONCLUSION: CD93 plays a critical role in tumor immune regulation. CD93 expression indicates more aggressive clinicopathological status and molecular subtypes of BLCA and worse therapy response, which implies that combing anti-CD93 therapy with immunotherapy (or chemotherapy) may be potentially beneficial for BLCA in clinical practice.	bladder
Metformin Can Enhance the Inhibitory Effect of Olaparib in Bladder Cancer Cells.	BACKGROUND: Bladder cancer is a common urinary system tumor. In the treatment of clinical patients, it is particularly important to find an effective treatment method to inhibit tumor growth. The world's first PARP inhibitor olaparib is mainly used for the treatment of BRCA1/BRCA2 mutated tumors. Metformin, an antidiabetic drug, has been reported to reduce cancer incidence in humans and improve survival in cancer patients. METHODS: Cell viability and proliferation were detected by CCK-8 assay and colony formation assay; cell apoptosis was detected by flow cytometry; cell migration and invasion abilities were detected by scratch assay and Transwell assay; STAT3/C-MYC signaling pathway protein were detected by western blotting. RESULTS: Olaparib combined with metformin has better effects on the proliferation, clone formation, migration, invasion, and apoptosis of bladder cancer cells than single drug, indicating that metformin can enhance the inhibitory effect of olaparib on tumor growth and regulate the expression of STAT3/C-MYC signaling pathway proteins. CONCLUSION: The results of this study showed that metformin could significantly enhance the antitumor effect of olaparib on bladder cancer cells, and these effects were mediated by downregulating STAT3/C-MYC signaling pathway proteins. This finding may have potential clinical application in the treatment of bladder cancer.	bladder
Surveillance and office management of low-grade Ta bladder tumors.	"OBJECTIVE: Patients with low-grade (LG), grade 1-2, Ta bladder cancer (BC) will frequently have a ""recurrence"". However, they rarely progress in stage. Although current guidelines mention surveillance and office management for these new or recurrent tumors, transurethral resection (TURBT) is the most common treatment. The purpose of this study is to determine if surveillance and/or office cautery is safe. MATERIALS AND METHODS: This study was conducted as a retrospective case series analysis of 45 patients who had recurrent LG Ta appearing bladder cancer (BC) and were managed primarily with surveillance and/or office cautery. Patients with carcinoma in-situ were excluded. The primary outcome was stage progression. RESULTS: Median follow up was 62 months. 41 (91%) patients did not progress in stage. Three patients recurred with HG T1 BC; one is receiving systemic immunotherapy. One patient developed HG T2 BC and was treated with a bladder preservation protocol. 40 (89%) patients underwent office cauterization. Eleven received BCG and 26 received post-cautery intravesical chemotherapy. Five (11%) patients developed HG BC during follow up. No patients died. None of the 17 (38%) Hispanic patients had progression. CONCLUSIONS: Active surveillance and/or office cautery for patients with small recurrent LG Ta bladder tumors is safe, reduces cost and improves quality of life by avoiding TURBTs."	bladder
Sex differences in treatment patterns for non-advanced muscle-invasive bladder cancer: a descriptive analysis of 3484 patients of the Netherlands Cancer Registry.	PURPOSE: Bladder cancer (BC) is a common malignancy with well-established differences in incidence, clinical manifestation and outcomes between men and women. It is unknown to what extent disparities in outcomes are influenced by differences in treatment approaches. This paper describes treatment patterns among men and women with muscle-invasive BC focusing on curative treatment (radical cystectomy or trimodal therapy). METHODS: A retrospective population-based cohort study was performed with data from the Netherlands Cancer Registry. All patients newly diagnosed with muscle-invasive, non-advanced BC (MIBC, cT2-4a, N0/X, M0/X) in the years 2018, 2019 and 2020 were identified. Patient and tumor characteristics and initial treatment were compared between men and women with descriptive statistics and multivariable logistic regression analyses. RESULTS: A total of 3484 patients were diagnosed with non-advanced MIBC in 2018-2020 in the Netherlands, of whom 28% were women. Women had higher T-stage and more often non-urothelial histology. Among all strata of clinical T-stage, women less often received treatment with curative intent (radical cystectomy [RC] or trimodality treatment). Among RC-treated patients, women more often received neoadjuvant treatment (except for cT4a disease). After adjustment for pre-treatment factors, odds ratios were indicative of women having lower probability of receiving curative treatment and RC specifically, and higher probability to receive NAC when treated with RC then men, although not statistically significant. CONCLUSIONS: Considerable differences in treatment patterns between men and women with MIBC exist. A more considerate role of the patient's sex in treatment decisions could help decrease these differences and might mitigate disparities in outcomes.	bladder
Association Between Sites of Metastasis and Outcomes With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma.	BACKGROUND: Sites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI. METHODS: We identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd(+) line. RESULTS: We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd(+) line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd(+) line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant. CONCLUSION: Bone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.	bladder
Severe and refractory hypocalcaemia secondary to osteoblastic bone metastases in bladder signet ring carcinoma: A case report and literature review.	RATIONALE: Symptomatic hypocalcaemia is uncommon, occurring in <2% of patients with malignancy. Osteoblastic bone metastasis as a cause of hypocalcaemia is rare and not reported in bladder cancer. PATIENT CONCERNS: We report a case of refractory hypocalcaemia in a patient with bladder cancer with extensive osteoblastic bone metastases. A 64-year-old male with a history of signet ring bladder carcinoma with osteoblastic bone metastases presented with severe hypocalcaemia with corrected calcium of 1.64 (2.09-2.46) mmol/L as well as hypomagnesemia and hypophosphatemia. He was previously treated with chemotherapy and immunotherapy. Denosumab was also initiated for the prevention of skeletal-related events. DIAGNOSES: Additional investigations showed significantly elevated bone formation markers N-terminal propeptide of type I procollagen and alkaline phosphatase. Chest radiography and computed tomography scan also demonstrated extensive areas of sclerotic bone lesions suggestive of osteoblastic bone metastases. He was diagnosed with severe hypocalcaemia secondary to osteoblastic bone metastases and partly to denosumab, vitamin D deficiency, and hypomagnesemia. INTERVENTIONS: He was treated aggressively with calcium and vitamin D replacement. OUTCOMES: Despite prolonged intravenous calcium replacement and high doses of oral calcium, cholecalciferol, and calcitriol replacement, he had persistent hypocalcaemia with calcium levels ranging from 1.8 to 1.9 mmol/L. He died 4 months after his admission. LESSONS: Osteoblastic bone metastases lead to an increased influx of calcium and phosphate into the bone leading to hypocalcaemia and should be considered as a differential in severe and refractory hypocalcaemia. It is rare and has not been described in bladder cancer. Precaution should be taken upon the initiation of antiresorptive in patients with osteoblastic bone metastases.	bladder
Management of hydronephrosis after radical cystectomy and urinary diversion for bladder cancer: A single tertiary center experience.	OBJECTIVES: To clarify the incidence of postoperative hydronephrosis and verify the validity of diagnostic and therapeutic approaches for hydronephrosis after cystectomy and urinary diversion for bladder cancer. METHODS: Totally, 290 patients receiving urinary diversion from 2005 through 2017 with complete data were enrolled, including 258 (89.0%) with an ileal conduit and 32 (11.0%) with an ileal neobladder. Postoperative radiographic images were reviewed. In patients with postoperative hydronephrosis, antegrade pyelography and ureteroscopy were performed to exclude malignant etiology. Balloon dilation and open surgical revision were performed according to the conditions. RESULTS: Forty-six patients (58 renal units) developed postoperative hydronephrosis. The cumulative incidence was 11.4% by a median follow-up of 59.5 months. Ureteral recurrence was detected by antegrade examinations in two patients, whereas malignant strictures were subsequently revealed in three patients. Thus, malignant etiology was found in hydronephrosis in five renal units (12.8%) of five patients (16.1%). The median times to diagnosis of hydronephrosis were 0 (interquartile range [IQR] 0-4) and 14 months (IQR 9-12) for benign and malignant strictures, respectively (p = 0.003). Of them, 31 patients (39 renal units) received interventions. Balloon dilation was performed in 13 renal units with benign strictures, and was successful in two (15.4%). Open surgical revision was performed in eight patients (11 renal units), including two with failed balloon dilation, all of which was successful. CONCLUSIONS: Postoperative hydronephrosis is potentially associated with recurrent disease. Accurate differential diagnosis is challenging although antegrade procedures may be helpful in some cases. Open surgical revision is highly effective to treat benign strictures.	bladder